ArticleMolecular and cellular biology2018
The VCP-UBXN1 Complex Mediates Triage of Ubiquitylated Cytosolic Proteins Bound to the BAG6 Complex.
Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- Inhibition of PGK1 enhances sensitivity to tyrosine kinase inhibitor in T315I-mutant leukemia.Acta pharmaceutica Sinica. B · 2026Article
- A conformation-dependent hydrophobic degron determines Rab9a-mediated vesicular trafficking.The Journal of biological chemistry · 2026Article
- Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for Drug Discovery.Proteomics · 2025Review
- Unraveling the Role of Proteinopathies in Parasitic Infections.Biomedicines · 2025Review
- BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells.Cellular & molecular immunology · 2024Article
- Article
- UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation.EMBO reports · 2024Article
- The role of RNF149 in the pre-emptive quality control substrate ubiquitination.Communications biology · 2023Article
- Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine.Frontiers in molecular biosciences · 2023Review
- Cooperative assembly of p97 complexes involved in replication termination.Nature communications · 2022Article
- A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Review
- Article
- Interactome screening of C9orf72 dipeptide repeats reveals VCP sequestration and functional impairment by polyGA.Brain : a journal of neurology · 2022Article
- Proximity proteomics of C9orf72 dipeptide repeat proteins identifies molecular chaperones as modifiers of poly-GA aggregation.Acta neuropathologica communications · 2022Article
- USP5 enhances SGTA mediated protein quality control.PloS one · 2022Article
- VCP/p97 cofactor UBXN1/SAKS1 regulates mitophagy by modulating MFN2 removal from mitochondria.Autophagy · 2022Article
- The p97-UBXN1 complex regulates aggresome formation.Journal of cell science · 2021Article
- VCP/p97 regulates Beclin-1-dependent autophagy initiation.Nature chemical biology · 2021Article
- AggreCount: an unbiased image analysis tool for identifying and quantifying cellular aggregates in a spatially defined manner.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A balance between protein synthesis and degradation is necessary to maintain cellular homeostasis. Failure to triage aberrant proteins may result in their accumulation and aggregation in the cytosol. The valosin-containing protein (VCP)-BCL2-associated athanogene 6 (BAG6) complex facilitates a wide variety of ubiquitin-mediated quality control events at the endoplasmic reticulum (ER), both prior to ER translocation and during ER-associated degradation (ERAD). However, how ubiquitylated clients associated with BAG6 are recognized by VCP for proteasomal degradation is presently unknown. We have identified UBXN1 as the VCP adaptor in BAG6-dependent processes occurring prior to ER insertion but not during ERAD. The loss of VCP-UBXN1 results in the inappropriate stabilization of ubiquitylated BAG6 clients and their accumulation in insoluble aggregates and sensitizes cells to proteotoxic stress. Our results identify how VCP is specifically targeted to ubiquitylated substrates in the BAG6 triage pathway and suggest that the degradation of ubiquitylated clients by the proteasome is reliant on the association of UBXN1 with ubiquitylated substrates and the catalytic activity of VCP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.